The overall objective of this proposal is to develop a model for studying human immune responses to neoantigens on cell surfaces. To this end we are utilizing techniques which we have developed for induction of human cell-mediated immune response in vitro to hapten-conjugated cells. We are studying both primary and secondary responses in a proliferative assay system. Most experiments utilize trinitrophenyl-conjugated cells. However, dinitrophenyl and fluorescein conjugates are studied also. The role of major histocompatibility complex genes and gene products in such responses will be of particular interest in two respects. First, we are investigating the possible role of HLA-associated Ir genes as determinants of responsiveness to hapten-conjugated cells. These studies will be performed in families, in an effort to associate high or low responsiveness with the inheritance of the HLA complex. Second, we are studying the role of HLA-antigens in induction and elicitation of responses to hapten-conjugated cells. Stimulator and responder cell populations involved in these responses will be characterized functionally, physically and for cell surface properties. These studies should provide fundamental insights into T cell recognition and response in humans and the role of major histocompatibility genes and antigens in such responses.